Mitochondrial disorders are associated with morphological neuromuscular junction defects

IF 2.7 4区医学 Q2 CLINICAL NEUROLOGY Neuromuscular Disorders Pub Date : 2024-10-25 DOI:10.1016/j.nmd.2024.105235

Lola E. R. Lessard , Emmanuelle Girard , Nathalie Streichenberger , Philippe Petiot , Cécile Acquaviva , Cécile Pagan , Peter Mulligan , Françoise Bouhour , Laurent Schaeffer , Arnaud Jacquier

{"title":"Mitochondrial disorders are associated with morphological neuromuscular junction defects","authors":"Lola E. R. Lessard , Emmanuelle Girard , Nathalie Streichenberger , Philippe Petiot , Cécile Acquaviva , Cécile Pagan , Peter Mulligan , Françoise Bouhour , Laurent Schaeffer , Arnaud Jacquier","doi":"10.1016/j.nmd.2024.105235","DOIUrl":null,"url":null,"abstract":"<div><div>We aimed to evaluate whether inherited mitochondrial dysfunction is associated with neuromuscular junction remodeling in patients with mitochondrial disorders.</div><div>Muscle biopsies from 15 patients with mitochondrial disorders and 10 control patients were analyzed through immunostaining for various neuromuscular junction components. The patient group, with a mean age of 49.9 years, exhibited various mitochondrial disorders including chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome, and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. Patients with mitochondrial disorders had a high percentage of remodeled (<em>p</em> <em>=</em> 0.0001), neoformed (<em>p</em> <em>=</em> 0.0049) and dilated (<em>p</em> <em>=</em> 0.016) endplates. There was a trend toward an increased proportion of neuromuscular junctions with terminal Schwann cell extension in these patients (<em>p</em> <em>=</em> 0.052). No significant difference was found in myofiber diameter between the groups. The observed neuromuscular junction defects varied widely across different mitochondrial disorder phenotypes and were present even without accompanying muscle weakness or neuropathy.</div><div>This suggest that mitochondrial disorders are associated with a primary NMJ remodeling independent of muscle structural damage. Pathomechanisms underpinning this remodeling of the neuromuscular junction, as well as clinical factors predictive of this remodeling, remain to be fully characterized.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"45 ","pages":"Article 105235"},"PeriodicalIF":2.7000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuromuscular Disorders","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960896624017310","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

We aimed to evaluate whether inherited mitochondrial dysfunction is associated with neuromuscular junction remodeling in patients with mitochondrial disorders.

Muscle biopsies from 15 patients with mitochondrial disorders and 10 control patients were analyzed through immunostaining for various neuromuscular junction components. The patient group, with a mean age of 49.9 years, exhibited various mitochondrial disorders including chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome, and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. Patients with mitochondrial disorders had a high percentage of remodeled (p = 0.0001), neoformed (p = 0.0049) and dilated (p = 0.016) endplates. There was a trend toward an increased proportion of neuromuscular junctions with terminal Schwann cell extension in these patients (p = 0.052). No significant difference was found in myofiber diameter between the groups. The observed neuromuscular junction defects varied widely across different mitochondrial disorder phenotypes and were present even without accompanying muscle weakness or neuropathy.

This suggest that mitochondrial disorders are associated with a primary NMJ remodeling independent of muscle structural damage. Pathomechanisms underpinning this remodeling of the neuromuscular junction, as well as clinical factors predictive of this remodeling, remain to be fully characterized.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

线粒体疾病与神经肌肉接头形态缺陷有关

我们的目的是评估遗传性线粒体功能障碍是否与线粒体疾病患者的神经肌肉接头重塑有关。我们通过免疫染色法分析了 15 名线粒体疾病患者和 10 名对照组患者的肌肉活检组织中的各种神经肌肉接头成分。这组患者的平均年龄为 49.9 岁，患有各种线粒体疾病，包括慢性进行性外斜视、Kearns-Sayre 综合征、线粒体脑肌病、乳酸酸中毒和中风样发作。线粒体疾病患者的内板重塑（p = 0.0001）、新生（p = 0.0049）和扩张（p = 0.016）的比例较高。在这些患者中，末端许旺细胞延伸的神经肌肉接头比例呈上升趋势（p = 0.052）。两组患者的肌纤维直径无明显差异。观察到的神经肌肉接头缺陷在不同的线粒体疾病表型中差异很大，甚至在没有伴随肌无力或神经病变的情况下也会出现。神经肌肉接头重塑的病理机制以及预测这种重塑的临床因素仍有待全面鉴定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Neuromuscular Disorders 医学-临床神经学

CiteScore

4.60

自引率

3.60%

发文量

543

审稿时长

53 days

期刊介绍： This international, multidisciplinary journal covers all aspects of neuromuscular disorders in childhood and adult life (including the muscular dystrophies, spinal muscular atrophies, hereditary neuropathies, congenital myopathies, myasthenias, myotonic syndromes, metabolic myopathies and inflammatory myopathies). The Editors welcome original articles from all areas of the field: • Clinical aspects, such as new clinical entities, case studies of interest, treatment, management and rehabilitation (including biomechanics, orthotic design and surgery). • Basic scientific studies of relevance to the clinical syndromes, including advances in the fields of molecular biology and genetics. • Studies of animal models relevant to the human diseases. The journal is aimed at a wide range of clinicians, pathologists, associated paramedical professionals and clinical and basic scientists with an interest in the study of neuromuscular disorders.